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Pathogenesis and Prognosis of Skin Diseases Caused by Host Immune Responses against EB virus Latent Infections

EB病毒潜伏感染宿主免疫反应引起皮肤病的发病机制及预后

基本信息

批准号：
17390311
负责人：
IWATSUKI Keiji
金额：
$ 9.15万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390311/
关键词：
EB virus latent infection reactivation host immunity lvmnhoma hvdroa vacciniforme HDAC inhibitor chronic active EBV infection NK T細胞宿主免疫応答ウイルス発がん蚊刺過敏症

项目摘要

1) The spectrum of EB virus (EBV)-associated NK/T-cell. lymphoproliferative disorders (LPD): We have registered cases with EBV-asscciated LPD as a reviewing center, and clarified the disease spectrum and the prognoses (Arch Dermatol 2006, Eur J Dermatol 2006). We have established a website registration system for cutaneous lymphomas, and began to collect the epidemiological data.2) Gene expression analysis using a noninvasive diagnostic method: We have established a noninvasive method using crusts for detection of latently infected EBV and cellular gene products (PATENT PCT/JP2006/317851). This method is available for analysis of other herpesvirus infections and cellular gene expression.3) Evidence for EBV reactivation in the skin legions, and alteration of latency patterns: Patients with severe diseases expressed a reactivation signal (BZLF-1 mRNA) in the skin lesions, while patients with mild diseases did not. In the mild disgase, however, LMP-1 expression levels were increased as compared with those in peripheral blood. 4) Analysis of EBV-infected cell line cells: We performed cytological analysis on the established cell lines. PMA and certain cytokines successfully induced reactivation in EBV-infected.NK/T-cell clones with a latent-infection cycle.5) Host immune responses: We found that pathogenic significance of host ea, responses against various EBV gene products was essential in the development of the skin lesions.6) Therapeutic approach: Host immune responses evoked to C/T antigens were analysed (Int J Cancer 2007). Immune ivasion mechanisms were studied in the same model (Cancer Immunol Immunother 2006). We found that some EBV-infected cells were sensitive to HDAC inhibitors. These observations may provide valuable data for immunopharmacological treatments for EBV-related LPD.7) We have drown out the version of guideline for cutaneous lymphomas including EBV-associaiated LPD.

1)EB病毒（EBV）相关的NK/T细胞谱。淋巴组织增生性疾病（LPD）：我们将EBV相关LPD病例登记为审查中心，并阐明了疾病谱和疾病（Arch Dermatol 2006，Eur J Dermatol 2006）。我们已经建立了皮肤淋巴瘤的网站登记系统，并开始收集流行病学数据。2）使用非侵入性诊断方法的基因表达分析：我们已经建立了使用痂检测潜伏感染的EBV和细胞基因产物的非侵入性方法（专利PCT/JP 2006/317851）。该方法可用于其他疱疹病毒感染和细胞基因表达的分析。3）EBV在皮肤军团中再激活和潜伏模式改变的证据：重度疾病患者在皮肤病变中表达再激活信号（BZLF-1 mRNA），而轻度疾病患者则没有。在轻度腹泻中，LMP-1的表达水平比外周血中的表达水平高。4)EBV感染的细胞系细胞的分析：我们对建立的细胞系进行细胞学分析。PMA和某些细胞因子成功地诱导了具有潜伏感染周期的EBV感染的NK/T细胞克隆的再活化。5）宿主免疫应答：我们发现宿主对各种EBV基因产物的应答的致病意义在皮肤病变的发展中是必不可少的。6）治疗方法：分析了对C/T抗原诱发的宿主免疫应答（Int J Cancer 2007）。在相同的模型中研究了免疫侵袭机制（Cancer Immunol Immunother 2006）。我们发现一些EBV感染的细胞对HDAC抑制剂敏感。这些观察结果可能为EBV相关LPD的免疫药理学治疗提供有价值的数据。7）我们已经制定了包括EBV相关LPD在内的皮肤淋巴瘤指南。